The authors have declared that no competing interests exist.
Chronic inflammation is known to be associated with both rotator cuff tears (RCTs) and depression. However, no epidemiological studies with a longitudinal follow-up have been performed to prove this association. We aimed to investigate whether depressed patients had an elevated risk of RCT and subsequent repair surgery compared with those without depression.
This retrospective cohort study comprised of patients diagnosed with depression between 2000 and 2010 (depression cohort) and patients without depression (non-depression cohort, 1:2 age and sex matched). The risk of RCT and rotator cuff repair surgery were determined during a 13-year follow-up (2000–2013) between these two cohorts.
This study included 26,868 patients with depression and 53,736 patients without depression. The incidence of RCT was 648 and 438 per 100,000 person-years in the depression and non-depression cohorts, respectively. The adjusted hazard ratio (HR) was 1.46 (95% confidence interval [CI], 1.36–1.57) for depressed patients. The incidence of rotator cuff repair surgery was 28 and 18 per 100,000 person-years in the depression and non-depression cohorts, respectively. Depressed patients also had a significantly increased risk of subsequent rotator cuff repair surgery (adjusted HR = 1.46; 95% CI, 1.04–2.06).
The present study showed that depression was associated with an increased risk of rotator cuff tear and rotator cuff repair surgery.
Recently, depressive disorders have been recognized as being associated with chronic systemic inflammation [
Rotator cuff tear (RCT) is a common disease associated with shoulder pain and functional disability, including shoulder motion limitation and weakness [
Although depression and RCT are both linked to chronic inflammation, epidemiological evidence for their association is lacking. Therefore, the present population-based, retrospective cohort study aimed to elucidate whether depression increases the risk of RCT, and the risk of subsequent rotator cuff surgery. The authors hypothesized that patients with depression would have an elevated risk of developing RCT and receiving subsequent rotator cuff repair surgery when compared with patients without depression.
The patient data for the present retrospective, nationwide cohort study was retrieved from the Taiwan Longitudinal Health Insurance Database 2005 (LHID2005). The LHID2005 includes the claims data of 1 million insurants, who have been randomly selected from the Registry of Taiwan National Health Insurance Research Database (NHIRD), which prospectively enrolls >23 million people (almost 99% of the population of Taiwan). The de-identified data recorded in the LHID2005 includes disease diagnostic codes (as specified by the International Classification of Diseases, 9th Revision, Clinical Modification [ICD-9-CM]), date of birth, gender, residential area, income, medication prescriptions and clinical procedures. The present study was approved by Chang Gung Medical Foundation Ethics Institutional Review Board (IRB CGMH 104-7528B) and complied with their ethical standards. The committee waived the need for written informed consent.
All patients listed in the LHID2005 with depressive disorders between January 1st 1997 and December 31st 2013 were identified (all ICD-9-CM diagnostic codes and National Health Insurance (NHI) procedure codes used in the present study are listed in
DEP, depression; Non-DEP, non-depression; LHID2005, Taiwan Longitudinal Health Insurance Database 2005.
To enhance the diagnostic accuracy, patients who were diagnosed as having depressive disorders before January 1st 2000 and who were diagnosed as having bipolar disorders were excluded. Patients younger than 18 years old and those who had a rotator cuff tendon tear before their diagnosis with depression were also excluded. The control cohort was randomly matched (1:2) from the remaining people in the LHID2005 without a history of rotator cuff tendon tear and depression by age and sex. The details of the study subject enrollment are shown in
The follow-up period was from January 1st 2001 until December 31st 2013. Any underlying comorbidities from before the index date of diagnosis were checked using the ICD-9-CM diagnostic codes. Chronic diseases, such as hypertension and DM were defined as repeated diagnosis in constitutive outpatient records when occurring within one year before the index diagnosis.
The main outcomes of this study were rotator cuff tear and rotator cuff repair surgery. The cases of rotator cuff tear were identified if they met the criteria of RCT by one admission claim or two following ambulatory claims. The diagnosis of RCT (ICD-9-CM 726.1, 727.61, 840.4) should have been determined by an orthopedic surgeon or a rheumatologist between January 1st 2000 and December 31st 2010 [
Baseline characteristics were compared between the two groups. The Chi-square test was used to analyze categorical variables. The risk of rotator cuff tendon tear and rotator cuff repair surgery between the two groups were compared using the Cox proportional hazard model, which was adjusted for all potential confounding variables listed in
Variables | Depression |
Non-depression |
|||
---|---|---|---|---|---|
n | % | n | % | ||
Gender | 1.00 | ||||
Male | 10,318 | 38.4 | 20,636 | 38.4 | |
Female | 16,550 | 61.6 | 33,100 | 61.6 | |
Age (years) | 1.00 | ||||
18–29 | 5,801 | 21.6 | 11,602 | 21.6 | |
30–39 | 5,798 | 21.6 | 11,596 | 21.6 | |
40–49 | 5,577 | 20.8 | 11,154 | 20.8 | |
50–59 | 4,277 | 15.9 | 8,554 | 15.9 | |
≥60 | 5,415 | 20.2 | 10,830 | 20.2 | |
Urbanization level | 0.52 | ||||
1 (City) | 8,499 | 31.6 | 17,241 | 32.1 | |
2 | 12,303 | 45.8 | 24,550 | 45.7 | |
3 | 4,191 | 15.6 | 8,226 | 15.3 | |
4(Villages) | 1,875 | 7.0 | 3,719 | 6.9 | |
Monthly Income (NTD) | < 0.01 | ||||
0 | 6,777 | 25.2 | 13,321 | 24.8 | |
1–15840 | 5,478 | 20.4 | 8,452 | 15.7 | |
15841–25000 | 9,039 | 33.6 | 18,933 | 35.2 | |
>25000 | 5,574 | 20.8 | 13,030 | 24.3 | |
Comorbidities | |||||
Diabetes mellitus | < 0.01 | ||||
No | 24,273 | 90.3 | 49,919 | 92.9 | |
Yes | 2,595 | 9.7 | 3,817 | 7.1 | |
Hypertension | < 0.01 | ||||
No | 20,724 | 77.1 | 44,973 | 83.7 | |
Yes | 6,144 | 22.9 | 8,763 | 16.3 | |
Hyperlipidemia | < 0.01 | ||||
No | 23,568 | 87.7 | 49,381 | 91.9 | |
Yes | 3,300 | 12.3 | 4,355 | 8.1 | |
Autoimmune disease | < 0.01 | ||||
No | 26,486 | 98.6 | 53,284 | 99.2 | |
Yes | 382 | 1.4 | 452 | 0.8 | |
Coronary heart disease | < 0.01 | ||||
No | 23,700 | 88.2 | 50,156 | 93.3 | |
Yes | 3,168 | 11.8 | 3,580 | 6.7 | |
Cancer | < 0.01 | ||||
No | 25,134 | 93.6 | 51,624 | 96.1 | |
Yes | 1,734 | 6.5 | 2,112 | 3.9 | |
Obesity | 0.03 | ||||
No | 26,733 | 99.5 | 53,556 | 99.7 | |
Yes | 135 | 0.5 | 180 | 0.3 | |
Gout | < 0.01 | ||||
No | 25,254 | 94.0 | 51,212 | 95.3 | |
Yes | 1,614 | 6.0 | 2,524 | 4.7 | |
Rotator cuff tear | < 0.01 | ||||
No | 25,507 | 94.9 | 51,859 | 96.5 | |
Yes | 1,361 | 5.1 | 1,877 | 3.5 | |
Rotator cuff tear need surgery | 0.01 | ||||
No | 26,808 | 99.8 | 53,657 | 99.9 | |
Yes | 60 | 0.2 | 79 | 0.1 |
NTD, New Taiwan Dollar.
Following application of the exclusion criteria, a total of 26,838 patients with depression (depression cohort) and 53,736 patients without depression (non-depression cohort) were included in the present study (
There were no significant differences in gender, age and urbanization level between the two cohorts (
Compared with patients in the non-depression cohort, patients with depression had a significantly higher incidence of RCT (incidence rate: 648 vs. 438 per 100,000 person-years;
The depression cohort had a significantly higher cumulative incidence of RCT than control cohort (
The depression cohort had a significantly higher cumulative incidence of rotator cuff repair surgery than control cohort (
Incidence of rotator cuff tear | Control Patients (n = 53,736) | Depression Patients |
---|---|---|
Events | 1,877 | 1361 |
Person-years | 428,743 | 209,938 |
Incidence per 100,000 person years | 438 | 648 |
Crude HR (95%CI) | 1.00 | 1.48 |
Adjusted HR |
1.00 | 1.46 |
CI, confidence interval; HR, hazard ratio.
a
b Adjusted for all covariates (gender, age, urbanization, income, and comorbidities including diabetes mellitus, hypertension, hyperlipidemia, autoimmune disease, coronary heart disease, cancer, obesity, and gout).
Incidence of rotator cuff tear | Control Patients (n = 53,736) | Depression Patients |
---|---|---|
Events | 79 | 60 |
Person-years | 436,278 | 215,722 |
Incidence per 100,000 person years | 18 | 28 |
Crude HR (95%CI) | 1.00 | 1.54 |
Adjusted HR |
1.00 | 1.46 |
CI, confidence interval; HR, hazard ratio.
a
b Adjusted for all covariates (gender, age, urbanization, income, and comorbidities including diabetes mellitus, hypertension, hyperlipidemia, autoimmune disease, coronary heart disease, cancer, obesity, and gout).
After adjustment for all covariates, depression was identified as an independent risk factor for rotator cuff tendon tear (hazard ratio [HR] 1.46, 95% confidence interval [CI] 1.36–1.57;
Variables | Crude | Adjusted |
||||||
---|---|---|---|---|---|---|---|---|
HR | 95% CI | HR | 95% CI | |||||
Depression | ||||||||
Yes | 1.48 | 1.38 | 1.59 | < 0.01 | 1.46 | 1.36 | 1.57 | < 0.01 |
No | 1.00 | Reference | 1.00 | Reference | ||||
Gender | ||||||||
Male | 0.80 | 0.74 | 0.86 | < 0.01 | 0.77 | 0.71 | 0.83 | < 0.01 |
Female | 1.00 | Reference | 1.00 | Reference | ||||
Age (years) | ||||||||
18–29 | 1.00 | Reference | 1.00 | Reference | ||||
30–39 | 2.77 | 2.32 | 3.32 | < 0.01 | 2.65 | 2.22 | 3.18 | < 0.01 |
40–49 | 6.16 | 5.21 | 7.27 | < 0.01 | 5.88 | 4.97 | 6.95 | < 0.01 |
50–59 | 8.31 | 7.03 | 9.82 | < 0.01 | 7.63 | 6.44 | 9.04 | < 0.01 |
≥60 | 6.44 | 5.44 | 7.62 | < 0.01 | 6.18 | 5.17 | 7.39 | < 0.01 |
Urbanization level | ||||||||
1(City) | 1.16 | 1.00 | 1.35 | 0.05 | 1.25 | 1.07 | 1.46 | < 0.01 |
2 | 1.11 | 0.96 | 1.29 | 0.17 | 1.19 | 1.02 | 1.38 | 0.02 |
3 | 1.04 | 0.88 | 1.22 | 0.66 | 1.08 | 0.92 | 1.28 | 0.35 |
4(Villages) | 1.00 | Reference | 1.00 | Reference | ||||
Income (NTD/month) | ||||||||
0 | 1.00 | Reference | 1.00 | Reference | ||||
1–15840 | 0.88 | 0.79 | 0.99 | 0.03 | 0.99 | 0.88 | 1.12 | 0.90 |
15841–25000 | 1.01 | 0.92 | 1.10 | 0.92 | 1.01 | 0.92 | 1.11 | 0.89 |
>25000 | 1.13 | 1.03 | 1.25 | 0.01 | 1.28 | 1.15 | 1.42 | < 0.01 |
Comorbidities (Yes/No) | ||||||||
Diabetes mellitus | 1.93 | 1.73 | 2.14 | < 0.01 | 1.16 | 1.03 | 1.30 | 0.02 |
Hypertension | 1.72 | 1.59 | 1.86 | < 0.01 | 0.90 | 0.81 | 0.99 | 0.03 |
Hyperlipidemia | 2.19 | 1.99 | 2.41 | < 0.01 | 1.31 | 1.17 | 1.47 | < 0.01 |
Autoimmune disease | 2.24 | 1.74 | 2.89 | < 0.01 | 1.51 | 1.17 | 1.95 | < 0.01 |
Coronary heart disease | 1.94 | 1.75 | 2.15 | < 0.01 | 1.19 | 1.06 | 1.34 | < 0.01 |
Cancer | 1.47 | 1.27 | 1.71 | < 0.01 | 1.01 | 0.86 | 1.17 | 0.95 |
Obesity | 2.62 | 1.78 | 3.85 | < 0.01 | 1.82 | 1.23 | 2.68 | < 0.01 |
Gout | 1.69 | 1.47 | 1.93 | < 0.01 | 1.17 | 1.02 | 1.35 | 0.03 |
NTD, New Taiwan Dollar.
a Adjusted for all covariates (gender, age, urbanization, income, comorbidities).
After adjustment for all covariates, depression was identified as an independent risk factor for RCT repair surgery (HR 1.46; 95% CI 1.04–2.06;
Variables | Crude | Adjusted |
||||||
---|---|---|---|---|---|---|---|---|
HR | 95% CI | HR | 95% CI | |||||
Depression | ||||||||
Yes | 1.54 | 1.10 | 2.15 | 0.01 | 1.46 | 1.04 | 2.06 | 0.03 |
No | 1.00 | Reference | 1.00 | Reference | ||||
Gender | ||||||||
Male | 0.94 | 0.67 | 1.33 | 0.74 | 0.95 | 0.66 | 1.36 | 0.78 |
Female | 1.00 | Reference | 1.00 | Reference | ||||
Age (years) | ||||||||
18–29 | 1.00 | Reference | 1.00 | Reference | ||||
30–39 | 6.60 | 1.49 | 29.22 | 0.01 | 6.14 | 1.38 | 27.27 | 0.02 |
40–49 | 17.75 | 4.26 | 73.98 | < 0.01 | 15.44 | 3.69 | 64.57 | < 0.01 |
50–59 | 30.06 | 7.27 | 124.25 | < 0.01 | 24.47 | 5.87 | 102.00 | < 0.01 |
≥60 | 30.59 | 7.44 | 125.71 | < 0.01 | 24.33 | 5.76 | 102.89 | < 0.01 |
Urbanization level | ||||||||
1(City) | 0.89 | 0.46 | 1.72 | 0.74 | 1.31 | 0.66 | 2.61 | 0.44 |
2 | 0.85 | 0.45 | 1.61 | 0.61 | 1.18 | 0.61 | 2.28 | 0.63 |
3 | 0.82 | 0.39 | 1.70 | 0.59 | 0.93 | 0.44 | 1.94 | 0.85 |
4(Villages) | 1.00 | Reference | 1.00 | Reference | ||||
Monthly Income (NTD) | ||||||||
0 | 1.00 | Reference | 1.00 | Reference | ||||
1–15840 | 0.62 | 0.34 | 1.15 | 0.13 | 0.71 | 0.38 | 1.32 | 0.27 |
15841–25000 | 1.27 | 0.83 | 1.93 | 0.28 | 1.42 | 0.90 | 2.22 | 0.13 |
>25000 | 0.88 | 0.54 | 1.45 | 0.62 | 1.17 | 0.68 | 2.00 | 0.57 |
Comorbidities (Yes/No) | ||||||||
Diabetes mellitus | 2.43 | 1.53 | 3.87 | < 0.01 | 1.10 | 0.66 | 1.84 | 0.72 |
Hypertension | 2.44 | 1.71 | 3.48 | < 0.01 | 0.89 | 0.57 | 1.40 | 0.62 |
Hyperlipidemia | 2.83 | 1.85 | 4.31 | < 0.01 | 1.30 | 0.80 | 2.12 | 0.29 |
Autoimmune disease | 2.49 | 0.79 | 7.82 | 0.12 | 1.45 | 0.46 | 4.58 | 0.53 |
Coronary heart disease | 3.40 | 2.26 | 5.13 | < 0.01 | 1.69 | 1.05 | 2.73 | 0.03 |
Cancer | 2.54 | 1.43 | 4.49 | < 0.01 | 1.52 | 0.85 | 2.71 | 0.16 |
Obesity | 2.25 | 0.32 | 16.08 | 0.42 | 1.45 | 0.20 | 10.45 | 0.72 |
Gout | 2.41 | 1.39 | 4.19 | < 0.01 | 1.30 | 0.72 | 2.34 | 0.39 |
NTD, New Taiwan Dollar.
a Adjusted for all covariates (gender, age, urbanization, income, comorbidities).
To the best of our knowledge, the present study is the first to investigate whether depression is associated with RCT and RCT repair surgery. The study revealed that patients with depression had a significantly higher risk of RCT and subsequent repair surgery compared with those without depression. After control for potential confounders, depression was shown to be associated with an increased risk of both RCT and the subsequent repair surgery. This suggests that patients with depression are at risk of developing rotator tendon injury and physicians should pay increased attention to their somatic complaints, particularly in association with their shoulders.
The underlying mechanism of how depression is associated with RCTs remains uncertain. The etiology of RCT could either be extrinsic (impingement and demographic factors) or intrinsic (degeneration, hypovascularity and inflammation) [
How do depression and the associated inflammation work together in tendon injury? Depression itself might not initiate the tear of rotator cuff tendons, however inflammation could potentiate the progression of tendinopathy and tearing [
Depression affects both the adrenocortical axis and hormone system and can impair pain perception [
In addition to chronic inflammation, it was found that comorbidities, including DM, hyperlipidemia and gout may also endanger the rotator cuff tendon in patients with depression. Patients with DM had a higher risk of overall tendon rupture [
There are several strengths to the current study. To our best knowledge, it is the first large database study to confirm the association between depression and RCT and cuff repair surgery. It also limited the depression cohort to individuals who were newly diagnosed with depression, and this made the calculation of time-to-event outcomes possible. Furthermore, both RCT and RCT repair surgery outcomes were followed, and the findings of the study indicated that the severity of RCT did not affect its significant association between depression. Three limitations were encountered during the present study. First, NHIRD does not provide details of medical imaging and the functional score of disease, which did not allow for quantitative analysis of the severity of rotator cuff tendon injury. Second, the incidence of rotator cuff tendon injury might have been underestimated. NHIRD could not record alternative therapies, such as acupuncture, traditional Chinese herbs, massage and manipulation, which are usually the primary treatments for patients with shoulder pain, especially in rural areas. Third, the diagnostic accuracy of rotator cuff tendon tear may be limited, although the study setting restricted the diagnosis of RCT to specialists, and applied the use of MRI and ultrasonography as validation. Other shoulder diseases, such as adhesive capsulitis may be confused with RCT due to the overlap of symptoms.
The present study is the first large-scale nation-wide retrospective cohort study illustrating the association between depression and rotator cuff diseases. Patients with depressive disorders were linked to a higher risk of RCTs and subsequent rotator cuff repair surgery. Further study is warranted to confirm whether there is a causal relationship between depression and RCTs.
RCT, rotator cuff tear; Non-RCT, non-rotator cuff tear; LHID2005, Taiwan Longitudinal Health Insurance Database 2005.
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The authors would like to thank the Health Information and Epidemiology Laboratory (CLRPG6G0041) for their comments and assistance in data analysis.